Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype

Mod Pathol. 2005 Mar;18(3):398-405. doi: 10.1038/modpathol.3800266.

Abstract

Primary breast diffuse large B-cell lymphoma has a poor prognosis relative to other extranodal diffuse large B-cell lymphoma. Recently, diffuse large B-cell lymphoma has been subclassified as germinal center B-cell-like and nongerminal center B-cell types using tissue microarrays. The 5-year overall survival rate of the germinal center B-cell group is better than that of the nongerminal center B-cell group. To elucidate the reason for which primary breast diffuse large B-cell lymphoma has a poor clinical outcome, we investigated 15 patients with primary breast diffuse large B-cell lymphoma (stage IE; 13 cases, stage IIE; two cases) by immunohistochemistry using various markers including CD10, Bcl-6, MUM1 and MIB-1 and by molecular analysis of the immunoglobulin heavy chain gene variable region. Immunohistochemistry showed 0/15 (positive cases/examined cases) for CD10, 5/15 for Bcl-6, 15/15 for MUM1, 10/15 for Bcl-2, 2/15 for CD5 and 4/15 for CD40. The expression pattern of CD10(-) MUM1(+) in primary breast diffuse large B-cell lymphoma corresponded to the nongerminal center B-cell group. Moreover, the MIB-1 index was distributed from 60 to 95% with a mean of 79%, indicating a high proliferation of the lymphoma cells. The immunoglobulin heavy chain gene variable region of primary breast diffuse large B-cell lymphoma had a mutation frequency of 1-10% (seven cases) and 0-1 additional mutations in ongoing mutation analysis (five cases). Primary breast diffuse large B-cell lymphoma had characteristics of the nongerminal center B-cell group. In conclusion, primary breast diffuse large B-cell lymphoma has a nongerminal center B-cell phenotype and has a high MIB-1 index. These features might therefore be associated with poor prognosis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD20 / analysis
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • CD40 Antigens / analysis
  • DNA-Binding Proteins / analysis
  • Female
  • Germinal Center / pathology
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunohistochemistry
  • Interferon Regulatory Factors
  • Ki-67 Antigen / analysis
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Middle Aged
  • Mutation
  • Phenotype
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors / analysis

Substances

  • Antigens, CD20
  • CD40 Antigens
  • DNA-Binding Proteins
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Interferon Regulatory Factors
  • Ki-67 Antigen
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors
  • interferon regulatory factor-4